3.1 Study Cohorts

In total, 1615 patients diagnosed with MM during 2015–2019 were included in the analyses. The mean age of the study cohort at diagnosis was 69.5 years, 29.5% were <65 years of age and 51.6% were male (Table 1). The average level of comorbidity measured by the CCI was 1.64. The cohort accumulated a total of 4387 patient-years during the first 5 years from diagnosis, the median follow-up time being 30.9 months. With respect to the end-of-life analyses, 417 and 505 patients were available for the analyses covering the last 12 and 6 months of life, respectively, with the median survival of 28.8 and 25.1 months. The number of patients who received palliative care before death was 145, which accounted for 25.1% of the 577 patients who died by the end of 2020, the mean time in palliative care being 2.6 months. Among these patients receiving palliative care, the median survival time from the first diagnosis was 30.8 months.

Table 1 Description of the study cohort3.2 Healthcare Resource Utilization and Service Use Patterns During the First 5 Years From Diagnosis

During the entire 5-year follow-up period, patients had on average 95.9 healthcare contacts per patient-year (PPY). More than half (59.5%) of total HCRU were in primary care, driven by home care visits. Less than one third (28.8%) of all HCRU were MM-specific. A large share of MM-specific healthcare contacts focused on specialized healthcare, accounting for around 84–92% of all specialized healthcare contacts during each year of follow-up (Table 2). A vast majority of all-cause (88–91%) and MM-specific (91–97%) specialized healthcare contacts were outpatient visits.

Table 2 All-cause and MM-specific healthcare resource use per patient-year during each year of follow-up

The number of total annual HCRU from any cause was highest during the first year from diagnosis (117 contacts PPY) (Table 2). The lowest number of contacts was observed during the third year (78 contacts PPY). After this, the number of contacts increased slightly up to 88 contacts PPY during the fifth year. There was a downward trend in the share of MM-specific healthcare contacts of total all-cause HCRU (34% in the first year and 24–27% in the following years). The highest relative decline was observed with MM-specific inpatient stays, the average number of which (PPY) reduced around 80% after the first year from diagnosis. Interestingly, the share of MM-specific inpatient stays decreased more in the specialized care setting.

3.3 Healthcare Resource Utilization and Service Use Patterns Before End of Life and During Palliative Care

All-cause and MM-specific HCRU per patient-month (PPM) during palliative care and the last 12 and 6 months of life are presented in Table 3. Within the last 12 and 6 months of life and during palliative care, patients had on average 15, 17 and 19 all-cause healthcare contacts PPM, of which 19%, 17% and 12% were MM-specific, and primary care accounted for 77%, 76% and 87% of the total HCRU, respectively. The most common healthcare contact was home care, accounting for 64%, 62% and 71% of all HCRU in the last 12 and 6 months and during palliative care, respectively. All-cause HCRUs increased towards a patient’s end of life in the primary care setting where, excluding inpatients stays, a minority of the contacts were defined as MM-specific. All-cause HCRU in specialized care during the last 6 months increased slightly compared with the last 12 months but decreased towards the time in palliative care. The decrease in all-cause specialized care contacts during palliative care was mainly driven by a decrease in outpatient visits.

Table 3 All-cause and MM-specific healthcare resource use per patient months during the last 12 or 6 months of life, and during palliative care

When converting the number of healthcare contacts PPM to contacts PPY, patients had on average 179 all-cause healthcare contacts, 137 primary care contacts and 42 specialized care contacts during the last 12 months of their life. When comparing the HCRU in the last year of a patient's life to the first year after MM diagnosis (Table 2), the number of total all-cause HCRU PPY increased by 53%, with an increase of 109% in all-cause primary care contacts and a decrease of 17% in all-cause specialized care contacts.

3.4 Healthcare Costs During the First 5 Years From Diagnosis

The mean healthcare costs were €46,000 PPY during the 5-year follow-up and 70% of the costs were MM-specific. Around 47% of all-cause and 57% of MM-specific costs originated from reimbursed outpatient medication and the rest of the costs from HCRU. The share of outpatient medication costs varied from 31% of all-cause and 36% of MM-specific costs during the first year of follow-up to 60% and 73% during the fifth year of follow-up. Both all-cause and MM-specific annual healthcare costs were the highest during the first year from diagnosis; €53,000 PPY and €36,000 PPY, respectively (Fig. 1). The lowest all-cause and MM-specific costs were observed during the third year of follow-up, after which the costs increased constantly.

Fig. 1

All-cause (A) and MM-specific (B) healthcare costs (€) per patient-year during each year of follow-up. MM multiple myeloma, PPY per patient-year

The mean HCRU costs PPY during the 5-year follow-up period were €25,000 and 58% of the costs were MM-specific. The costs were the highest within the first year of diagnosis (€37,000 PPY), being approximately twofold compared with the following years (Fig.1). Within the first year of diagnosis, 63% of the HCRU costs were MM-specific, with the share reducing to 48%–52% in the following years. Although most all-cause healthcare contacts focused on the primary care setting, specialized care was responsible for most of the all-cause HCRU costs, accounting for 86% (€31,000 PPY) of the total HCRU costs in the first year, and approximately 79% (€14,000–€15,000 PPY) of the total HCRU costs during the following years. In particular, although it was the most common all-cause healthcare contact, home care in the primary care setting only accounted for 5–9% of the all-cause HCRU costs PPY during the follow-up. The main cost drivers in both all-cause and MM-specific HCRU costs were outpatient visits and inpatient stays in specialized care. Within the total MM-specific HCRU costs, the share of specialized care costs ranged between 92% and 94% during the 5-year follow-up, driven by specialized care outpatient visit costs.

During the 5-year follow-up period, the total mean costs of reimbursed outpatient medication PPY were approximately €22,000, of which 86% were MM-specific. Lenalidomide accounted for 75% of total reimbursed outpatient medication costs, followed by pomalidomide with 8% (Supplementary Table 1, see electronic supplementary material [ESM]). During the first year from diagnosis, the total costs of reimbursed medication PPY were €16,000, increasing to €24,000 for the second year from diagnosis, and to €28,000 for the fifth year from diagnosis (Fig 1). During the first year from diagnosis, lenalidomide accounted for 77% (€19 million total/€13,000 PPY) of total reimbursed medication costs, with the share increasing to 82% (€24 million total/19,000 PPY) during the second year from diagnosis. The mean PPY costs and the share of the total costs of lenalidomide began to decrease after the second year of diagnosis, being €18,000 (75%), €17,000 (66%) and €16,000 (57%) in the third, fourth and fifth year from diagnosis, respectively.

3.5 Healthcare Costs Before End of Life and During Palliative Care

The mean healthcare costs PPM within the last 12 and 6 months of life and during palliative care were €5400, €6100 and €4900 (Fig. 2), and 63%, 59% and 51% of these costs were MM-specific, respectively (Fig. 2). The share of outpatient medication costs of all-cause healthcare costs was 41%, 34% and 8% within the last 12 and 6 months of life and during palliative care, respectively. When converting the healthcare costs within the last 12 months of life to costs PPY, total all-cause healthcare costs during the last year of life (€60,000 PPY) were higher compared with total PPY costs accumulated within the first year of MM diagnosis (€53,000 PPY).

Fig. 2

All-cause (A) and MM-specific (B) healthcare costs (€) per patient-month during the last 12 or 6 months of life, and during palliative care. MM multiple myeloma, PPM per patient-month

The mean all-cause HCRU costs PPM within the last 12 and 6 months of life and during palliative care were €3200, €4000 and €4500 (Fig. 2), with specialized care accounting for 69%, 68% and 44% of the total costs, and 49%, 48% and 54% of the total costs categorized as MM-specific, respectively. The share of MM-specific HCRU costs PPM in primary care were larger during palliative care compared with the last 12 and 6 months before death. In both specialized care and primary care, the total mean PPM costs within all contact categories increased in the last 6 months of life compared with the last 12 months of life. Compared with the 12 and 6 months before death, the mean HCRU costs PPM during palliative care increased in primary care and decreased in specialized care. The highest PPM HCRU cost increase during palliative care compared with the last 12 and 6 months of life was seen in the primary care inpatient stay costs, and the highest reduction was in the specialized care outpatient visit costs. The main cost driver in all analyzed timeframes was inpatient stays (in primary and specialized care combined), accounting for 47% (€1500 PPM), 53% (€2100 PPM) and 67% (€3000 PPM) of total PPM costs for the last 12 and 6 months before death and during palliative care, respectively.

The total mean reimbursed outpatient medication costs PPM for the last 12 months of life were approximately €2000 (or €27,000 PPY), of which lenalidomide accounted for 55%, pomalidomide for 23% and ixazomib for 5% (Supplementary Table 2, see ESM). The respective figures for the last 6 months of life were €2000 PPM, 50%, 24% and 6%. Reimbursed outpatient medication costs during palliative care were €403 PPM, being mainly associated with non-MM medication (lenalidomide was associated with 18%, and pomalidomide and ixazomib with 0%).

3.6 Reimbursed Sick Leave and Associated Costs

The study cohort accumulated a total of 46 reimbursed sick leave days PPY within the first year from diagnosis but the number declined drastically during the following years (Supplementary Table 3, see ESM). During the 5-year follow-up, a vast majority (90%) of sick leave days were associated with MM. It should be noted that the data on sick leave were based on a Kela register on paid reimbursements where sick leave is recorded only after a 9-day waiting period. Thus, these numbers are underestimations as short-term sick leave, lasting 1–9 days, is not accounted for. The mean amount of paid sick leave reimbursements during the first year of diagnosis was €3000 PPY. A significant reduction in paid sick leave reimbursements was seen after the first year with amounts ranging between €136 and €269 PPY during the following years. Reimbursed sick leave days and associated costs were minimal during end of life (Supplementary Table 4, see ESM).